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- Song, Jie, et al.
(författare)
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Similar familial risk in multiple sclerosis subgroups
- 2017
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Ingår i: Multiple Sclerosis. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1352-4585 .- 1477-0970.
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Tidskriftsartikel (refereegranskat)abstract
- Background: A subgroup of patients diagnosed with multiple sclerosis (MS) present with no oligoclonal bands (OCB) in the cerebrospinal fluid (CSF). Several studies report different clinical characteristics and genetic associations between the two groups. Objective: To investigate whether the OCB negative subgroup has a distinct etiology from band positive MS. Methods: Using nationwide registers to estimate familial risks, which reflect the genetic contribution of a disease. Results: Odds ratios of MS were similar for relatives to band positive and negative patients. Conclusion: From the perspective of familial liability, MS without OCB is etiologically closely related to the dominant subgroup of OCB positive MS.
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- Binzer, S, et al.
(författare)
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Genetic analysis of the isolated Faroe Islands reveals SORCS3 as a potential multiple sclerosis risk gene
- 2016
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 22:6, s. 733-740
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Tidskriftsartikel (refereegranskat)abstract
- In search of the missing heritability in multiple sclerosis (MS), additional approaches adding to the genetic discoveries of large genome-wide association studies are warranted. Objective: The objective of this research paper is to search for rare genetic MS risk variants in the genetically homogenous population of the isolated Faroe Islands. Methods: Twenty-nine Faroese MS cases and 28 controls were genotyped with the HumanOmniExpressExome-chip. The individuals make up 1596 pair-combinations in which we searched for identical-by-descent shared segments using the PLINK-program. Results: A segment spanning 63 SNPs with excess case-case-pair sharing was identified (0.00173 < p > 0.00212). A haplotype consisting of 42 of the 63 identified SNPs which spanned the entire the Sortilin-related vacuolar protein sorting 10 domain containing receptor 3 ( SORCS3) gene had a carrier frequency of 0.34 in cases but was not present in any controls ( p = 0.0008). Conclusion: This study revealed an oversharing in case-case-pairs of a segment spanning 63 SNPs and the entire SORCS3. While not previously associated with MS, SORCS3 appears to be important in neuronal plasticity through its binding of neurotrophin factors and involvement in glutamate homeostasis. Although additional work is needed to scrutinise the genetic effect of the SORCS3-covering haplotype, this study suggests that SORCS3 may also be important in MS pathogenesis.
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| 10. |
- Binzer, S, et al.
(författare)
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High inbreeding in the Faroe Islands does not appear to constitute a risk factor for multiple sclerosis
- 2015
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 21:8, s. 996-1002
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Tidskriftsartikel (refereegranskat)abstract
- Large population-based genome-wide association studies have identified several multiple sclerosis (MS) genetic risk variants, but the existing missing heritability warrants different strategies. Isolated populations offer an alternative way of searching for rare genetic variants and evaluating the possible role of consanguinity in the development of MS. Studies of consanguinity and MS risk have yielded conflicting results. Objectives: In this study we investigated the role of consanguinity on MS risk in the relatively isolated Faroe Islands, which have a presumed high level of inbreeding. Methods: A total of 29 cases and 28 matched controls were genotyped and assessed for inbreeding coefficients, number of runs of homozygosity (ROH) at different lengths and observed number of homozygotes as measures of relatedness. Parametric and non-parametric statistical models were applied. Results: Both cases and controls exhibited considerable relatedness demonstrated by very high inbreeding coefficients, large number of observed homozygotes and many long ROH. However, apart from the number of ROH ≥ 2.5 mega base pairs, no significant differences between the two groups were observed. Conclusions: Overall, no significant difference between cases and controls were found, indicating that consanguinity in itself does not appear to be an important risk factor for MS in the population of the Faroe Islands.
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